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Development of the First Genetically Humanized Mouse Model for Hepatitis C Virus Infection

Worldwide, an estimated 180 million people are infected with the hepatitis C virus (HCV), and 75 percent of those will develop chronic liver disease. There is no vaccine available, and antiviral treatment is only partially effective. The lack of treatments is due in part to a lack of suitable, reliable small-animal models for laboratory studies of the disease.

Previously, to study HCV infection in small animals, researchers transplanted human liver cells into mice with compromised (impaired) immune systems. Though helpful in the study of viral biology, the method makes it impossible to study the immune responses to HCV. Experimental models using laboratory-grown cells were not available either, until NIAID-funded investigators demonstrated that mouse cells could be infected with HCV when they express two human proteins: CD81 and occludin.

Building on this success, the researchers created immune-competent mice (mice with healthy immune systems) that produced these two human proteins in their liver cells. This approach made the mice susceptible to HCV infection.

This experimental system will allow researchers to study how HCV causes disease and the immune response to the virus in a small animal. In addition, novel molecules that block HCV entry into cells can be evaluated in a live animal. Looking further, these mice could be used to evaluate experimental HCV vaccines and other therapies in preparation for human studies.